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Author
Topic: Can Resistance Still Occur Even With 100% Adherence? (Read 27490 times)

I've read quite a lot about resistance and I'm not completely sure I understand it.

From what I've read, it seems like it works in a similar way to evolution/natural selection. That is to say that a mutation during the process of reproduction may lead to a variant of the virus that enables it to survive in conditions that the other forms of the virus can not. Hiv meds practically stop, or at least drastically slow down, the reproduction of the virus, thus limiting the amount of mutations that can conceivably occur. Have I got this bit right?

However does this not mean that, even with dramatically reduced reproduction, there is still the possibility of a mutation occuring, rendering it resistant to the meds you are currently taking, even if you take the meds every single day.

I find it a little discouraging to think that I could still get resistance even with total adherence.

.................................. there is still the possibility of a mutation occuring, rendering it resistant to the meds you are currently taking, even if you take the meds every single day.

I find it a little discouraging to think that I could still get resistance even with total adherence.

Reality bites, doesn't it?

Yes, is the answer you are going to get from me. I have been on meds since 1994, and my virus has mutated through most of the medications. I am not totally out of options, but here we are in June of '06, and my virus is again mutating after five full years of stability. My adherence has been in the 99% range for all of the past 12 years, but the way this virus works, there is little hope that we will be able to STOP the virus mutations in the near term. I am hopeful that the drug companies will continue to work towards a cure, but hell, at 59; and having lived with this bug since 1983, I am very happy with the fact that I am still here, still stirring the pot, and trying to make a difference in this world.

Here's to coctails.

In Love and Support.

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The Bible contains 6 admonishments to homosexuals,and 362 to heterosexuals.This doesn't mean that God doesn't love heterosexuals, It's just that they need more supervision.Lynn Lavne

This past week I've read a few things that sort of threw me for a loop. The PBS Frontline report states that resistance can occur in as little as 3-5 years, and the quiz on their website says that the meds extend life for an average of eight years. (Since I just started year 12 on the meds, I found this news a little depressing.) Then you read on, and they seem to be talking about developing countries, where oftentimes only a few of the cocktail combinations are available.

I'll be watching this thread, because the more I read, the more I don't know what to think.

I have alway adhered to my drug regimen since I started in 89. I have been undectable only once, about three months ago,but I am resistant to those drugs now. I rarely have a regimen last longer than 1 year. Usually in about 6 months they are history. Everyone is different.

So it seems like meds, by their nature of slowing down reproduction, also reduce the risk of mutations occuring, but it's still eminently possible. A little discouraging but I guess I have to think positive and look at the better odds with meds than without.

Can I ask Jack, if your regimens have generally lasted so shortly, what options are available to you at the moment? It sounds like you would burn through most of the tablets if they last at most a year.

Your analysis of resistance is pretty much right. That's the problem with current HIV therapy. The response to the problem is two fold. Firstly there is a need to come up with new medications that are reactive against current resistance strains. This is a short-term solution but a do-able one. However, that way of treating HIV is like that carnival game where the mole pops up it's head and you smash it with a mallet. It's not a viable way to cure the disease. So everyone is working on better stratagies. One method is to try and find where HIV is replicating when people are on HAART and design things to hit it there. The final solution would be some sort of treatment that can stimulate the immune system to take over from current drug therapies and keep patients off medication for years.

R

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

As I understand it, since the meds are unable to reach every single organ/area in your body, HIV can and does replicate, (albeit probably very minimally), in certain parts of your body where drug levels aren't high enough to completely stop viral replication (for example your prostate or sometimes the brain/central nervous system). As those viruses, (replicating in small numbers in certain organs), start to collect mutations, they can eventually create a mutated virus capable of replicating despite the presence of your drugs. That mutated virus is then free to roam outside of the reservoir that created it and replicate elsewhere, (i.e., you are no longer undetectable). Though when and how often that happens is probably unknown (or rather, not something you can estimate since it varies from person to person/infection to infection).

You can't control that aspect of HIV. But you can focus on reducing the chances of resistance occurring because of skipped dosages, (which probably happens much, much more frequently and is a much easier option for the virus to gain resistance). Take your meds on-time, everyday, then you have done your part. And that's all you can do.

I have what may be a dumb question. Regarding the areas of the body where HIV can hide during HAART, is it nor possible to inject some sort of anti-retroviral med into those areas? Granted, I'd be more comfortable with an injection into my prostate than one into my brain, and maybe we'd have to have a whole different type of drug. I'm just curious.

I have what may be a dumb question. Regarding the areas of the body where HIV can hide during HAART, is it nor possible to inject some sort of anti-retroviral med into those areas? Granted, I'd be more comfortable with an injection into my prostate than one into my brain, and maybe we'd have to have a whole different type of drug. I'm just curious.

Anyone know where else the virus is likely to hide?

S

I dunno....never thought about that one. Though there would probably need to be a cost/benefit analysis. It still wouldn't clear HIV infection (since that's due to latent cells). It may just result in lower resistance (in terms of resistance created despite complete adherence to oral meds)...but that may not be that significant enough to worry about.

Plus you would likely have to do the injection in multiple places on a daily basis. Daily injections into your brain/central nervous system, doesn't sound very pleasing (nor safe for that matter). I reserve judgment on the prostate one. Perhaps that might have its benefits.

Cliff's analysis is very wise here. Injecting anything daily is a bad idea - just ask anyone who takes Fuzeon. It's not a viable therapy and the benefits of doing it might be outweigh the cost to the patient in terms of comfort and money (injections are more expensive). The other thing is really we don't know where HIV is hiding - there are a few good ideas - but it's hard to measure. This is indeed a focus of much research. One obvious place is the CNS/brain, as it has been hard to get all the medication there because of the blood/brain barrier. Another thing to think about is that not all cells take up the drug to the same amounts (here I am not talking about within a population of CD4+ lymphocytes but other cells that can be infected by HIV or take up the virus like DC's). Drug coverage in these areas is another area that needs to be looked at that could improve the resistance profile of many existing drugs. Again, these are all short term measures to improve existing therapy, but ultimately the key lies in getting people off therapy. I can't stress how important a goal that is and how hard we must work to achieve it. In the mean time, the above measures should help improve the lives of those who have to take HAART while we figure out what to do.

R

PS. Cliff, I am taking a lunch break right now, so I'm not stopping working just to be on this forum.

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

I asked my HIV specialist and my ID specialist this exact same question. Both of their answers pretty much said this -- in 90-95% of cases, resistance is caused due to non-adherance to the med schedule. The rest of the time it just happens naturally. Although my HIV specialist stated he felt that it was probably closer to 98% of the time mutation occurs due to lack of adherance.

I take my meds as scheduled, ALWAYS. I follow the rules of no antacids (reyataz does not like them) and I take them with a meal or snack. It is a burden at times but I am not giving this sh1tty virus even one chance at mutating since I am already resistant to the class of drugs that include Sustiva.

So, after one year I am undetectable (and have been for six months) and hope to stay that way.

So when people are diagnosed with resistance prior to starting meds, is that usually because of the person who infected them already having the resistance?

I may be barking up the wrong tree here, but if someone goes years before they start meds, does that not increase the chance that they will develop a resistant form of the virus before they have even taken a pill?

So when people are diagnosed with resistance prior to starting meds, is that usually because of the person who infected them already having the resistance?

I may be barking up the wrong tree here, but if someone goes years before they start meds, does that not increase the chance that they will develop a resistant form of the virus before they have even taken a pill?

I feel like I'm back in Science class lol

yes, according to my doc, I was infected by someone who was already resistant. my doc said about 10% of new infections in my county are this way. as for the second part of your questions I am not sure that is how it works, but I am just a flight attendant not a doctor.

(1) It's there already.(2) It evolves because the drugs do not assert enough presure to keep your HIV infection under control, and it learns to adapt.

An HIV infection is a mix of different strains of HIV, some "fitter" than others. One (or a few) tend to dominate. This mix may include a strain with a mutation that makes a particular drug less effective against it. This means that an otherwise weedy, hidden strain can emerge when you start treatment cos the drugs have hammered the rest, but it has escaped extermination.

Another reason for resistance developing is not taking the drugs on time and all the time. This lets the virus(es), er, learn to adapt to the drugs and bud off new HIVs that aren't affected by them (or perhaps not affected as much). In time, if you stay on the same drugs, these will come to dominate and your viral load shoot up... (this is called "viral breakthrough").

However, resistance is not inevitable... and not always important...

If your viral load is less than 50 copies (undetectable) the chances of a resistant strain emerging are very low.

If your combo gets you viral load undetectable and keeps it there, then you can use the same drugs for many years, potentially indefinitely.

Acording to my Dr. resistance should not occur with a 100% adherence. A friend of mine who has been positive for 12 years has always been undetectable. This is his 10th year being undetectable. He has switched meds due to side effects but never for resistance issues. Anyway he is very responsible and just started studying to become a nurse.

You also need to take into account, what the long term effects these meds have on your organs...Liver, Pancreas... Not everyone can take all the meds that are available, even if you are not resistant to them, they simply can not be tolerated. vThe only hope is additional research for safer medications.

<<Acording to my Dr. resistance should not occur with a 100% adherence.>>

Apparently a lot of doctors say this. They are wrong. Moffie's post underscored this perfectly. The reason that statement bothers me is that it creates a situation where the patient is blamed, or shamed, by the doctor (or his fellow pozzies) when a drug regimen fails. Sometimes HIV mutates out from under a successful drug regimen. And the science behind HIV supports this.

When doctors place a burden on their patients to the tune of 98% adherence and toxic, life/personality/body changing side effects, pit them against a virus that mutates as fast as any virus ever studied, and then even insinuates that the patient is at fault for a drug resistance, it makes me testy. It creates an adversariual relationship that is anethema to progressive and optimistic treatment.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

Justin, steering clear of the meds because of potential side effects and eventual resistance is a little like not dating until you have planned the wedding. Nothing lasts forever, or works perfectly. And not everyone has the same experience.

The key is to stay alive until the next breakthrough. And then the next. and then the next.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

My doctor says the same thing about adherence as other people up top have said and if you are really adherent and treatment naive with little to no resistance, your chances of developing resistance are VERY LOW.

That's a fact based on studies and pans out in statistical analysis.

Optimistic I received a PM a few months ago from someone who said some of what he read from others about the meds and sides and resistance got him so scared that he ignored the situation and in that time developed extreme anemia from teh virus and came close to death. When he got on the meds he had no sides and he is doing well today and could kick himself for living in fear and not verifying.

Remember that what you read when it comes to medical advice on here sometimes is not always rooted in fact. You need to verify.

I'm a believer in having a good doctor who really knows his stuff and will give you the facts. And also remember that starting meds in 2006 is a whole different ballgame than those who started when HAART first came out.

STAY OPTIMISTIC!!!!!

And don't succumb to fear if you can avoid it.

Hope is important, and many of us are hopeful that we can and will live long lives and manage this disease on a daily basis. I don't base this on wishful thinking, but the facts.

Best,Mikey

« Last Edit: June 06, 2006, 10:15:22 PM by StrongGuy »

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

It is my belief that even on a dedicated 100% regimen, one will eventually become resistant to it.

It is my understanding that the way the virus mutates over time may cause this even in non-resistant and with 100% adherence... I think it's just a factor of time.

Whether that be many years or a few years, I think it is the eventual outcome of all meds.

Please post links to your 'facts'.

Luckily in this day and age, we have many treatment options... but not nearly enough or effective enough for all.

But for the original poster, don't be afraid of starting meds because of resistance... new drugs will be coming down the pipeline. It's important not to 'burn thru' the options, but taking meds for an average person will give them very many years of health. and if you ever become resistant to them all... there will be more meds... adherence is definitely very important but by the time you might burn thru all the meds, at least 10 years will have passed and we will have some new options hopefully. (not to say you will burn thru them... but adherence is important)

Based on ten years of data available, and looking at highly adherent individuals with maintained undetectable viral loads, I was told the data shows their chances of future resistance is very low. My doctors over the years who've said the same thing could be lying, but I doubt it and trust them

Dingoboy you should definitely verify and I'm sure if you check with your doctor or people in the field they hopefully they can pull up the information for you. (not my job or desire to do it for you.)

I'm also skeptical of much of what I read here too from people when it comes to medical advice and look for answers based on facts and scientific statistical studies, not anecdotal observations or feelings.

Happy searching...Best,Mikey

« Last Edit: June 06, 2006, 10:48:30 PM by StrongGuy »

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

I'm glad your doctors told you that and you trust them. It's imperative to have a good relationship with your doctor.

Quote

Dingoboy you should definitely verify and I'm sure if you check with your doctor or people in the fieldthey hopefully they can pull up the information for you. (not my job or desire to do it for you.)

Actually, if you wish to make claims of 'fact' here, it IS your responsibility to post references for it. Till then, it must be presumed as your opinion. As I stated in my response to you.. it is my opinion that resistance will eventually develop regardless of what one does.

You state supposed facts without any references or sources and even did so in bold as if it makes it that much more factual. Well, bold doesn't make it more factual. It still remains your opinion and only your opinion, which you are entitled to.

You don't want to believe it or want to call it an opinion, do whatever your heart desires. I couldn't care less.

And seriously don't tell me how or what I should post or my use of BOLD letters. Since when are you the diary police?

I'll post whatever I please and use whatever words I want anytime of the day dingoboyboy.

Peace and love Mikey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

Strong, surely you realize that in the same post where you dismiss anecdotal evidence, you choose not to provide quantification, thus providing, well, anecdotal evidence.

Which is legitimate in a support forum, absolutely. But it provides little in the way of data.

Also, like I mention, it more than implies culpability - even blame - on the part of the patient, which should absolutely not be encouraged.

I feel badly for people who, based on reading the personal experiences here on aidsmeds, become too frightened to care for themselves. I do not, however, believe that the answer should be to censor ourselves or each other. Should those of us who have been sick refrain from discussing our situations for fear of scaring others? Most of us are careful to point out that our experiences are our own, and that other people's mileage might vary. This site is dedicated to facts. Some of them are sobering. But honesty should take precedence.

I believe it is important to quantify answers, especially when discussing a scientific topic.

The plural of anecdote is not data.

Just saying.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

You and dingoboyboy who don't get along with me and any others can choose to not believe me and I wholeheartedly understand and I believe everyone should verify what anyone says regarding medical advice or HIV population assumptions with their doctors or people in the scientific field. That's very important because there is at times muchf misinformation from people on here.

If you think I should provide a link to studies that my doctors cited in his office for which a layman like me has no link to, well then your poop out of luck on that one.

Sorry

Love ya Mikey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

You don't know it's a fact. You are going by what other people (even though they may be doctors) have told you. You don't know it 'pans out' in statistical analysis, because, as is obvious to the rest of us, you haven't seen those studies.

Quote

You and dingoboyboy who don't get along with me and any others can choose to not believe me and I wholeheartedly understand and I believe everyone should verify what anyone says regarding medical advice or HIV population assumptions with their doctors or people in the scientific field. That's very important because there is at times muchf misinformation from people on here.

If you think I should provide a link to studies that my doctors cited in his office for which a layman like me has no link to, well then your poop out of luck on that one.

It's very important to verify information, which you apparantly haven't done. I fail to understand why you would state something as 'fact' that you obviously have no method of knowing. If you had stated 'my doctor told me...', I would not have disagreed with you, as that is your experience, but you chose to state something as fact when you have no idea if it is or isn't. Flat out, you are wrong in your statements of 'fact' when you have no idea of their validity.

So, essentially, you are going upon your opinion and your opinion only. Just like I am which I did state that it was only my opinion that 'resistance is inevitable'.

I feel you are entitled to your opinions. We all are and that is a blessing on this forum, but if you choose to state something as fact here, please be prepared to back it up... which, frankly, you cannot or are unwilling to do, so your initial statement of the 'fact' must be completely dismissed.

And my name is Dingoboi... learn it, love it or don't bother mentioning it. I presume you are using a purposeful misspelling of my name to 'annoy' me. You have done it several times before and, frankly, it's kinda sad that you use such tactics.

<< There have been some studies showing that resistance develops even at undetectable levels. Others show it can occur even with 100% adherence. Researchers are searching for the mechanisms that allow this to happen.>>

<< there is some evidence that resistance can emerge slowly in people with undetectable viral load. Studies into long-term suppression of HIV due to antiretroviral therapy have found evidence of viral replication and mutation (Furtado 1999; Zhang 1999). It is now believed that antiretroviral therapy cannot eradicate HIV from the body completely, and that HIV continues to reproduce at low levels despite treatment. This raises the prospect of resistance emerging even among people with very low levels of HIV in their blood. This may, in turn, lead to treatment failure and viral rebound.

A Swedish group confirmed that resistance mutations do emerge among people with viral loads between 50 and 500 copies/ml (Soderborg 1999). >>

Perfect adherence greatly extends the life span of an antiviral regimen, but it appears that most of us will develop some resistance at some point, regardless. The key seems to be holding it off as long as possible, while newer and better therapies are developed.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

Your data verifies an aspect of this discussion I never disagreed with.

Like I said, the data I was shown shows the development of resistance with undetectable viral loads and high adherence is VERY LOW based on teh ten years of knowledge we have from HAART.

No one is saying resistance can't happen and will happen to people in this segment of the population. I'm just saying it's very low.

Isn't The Body a great resource? I have access to the Body Pro too which is even better.

I'm in LOVE with Dr. Pierone and Doctor Daar. They are my Idols.

Good stuff...

Love ya Mikey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

For many, many people, one regimen lasts for years and years. Decades even.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

There have been some studies showing that resistance develops even at undetectable levels. Others show it can occur even with 100% adherence. Researchers are searching for the mechanisms that allow this to happen.

Although I have been undetectable for 3 years I explained to my Dr how I still could still "feel" the virus in my system. I told her about my memory lapses and sometimes just a total feeling of being "lost in space." I told her I had this feeling that the virus plays "Hide and Seek" when it comes to test for the viral load. She told me there are places deep in the crevices of the mind that HAART cannot access.

Quote

there is some evidence that resistance can emerge slowly in people with undetectable viral load.

I think that's what happens when you can't flush your system completely clean.

Perfect adherence greatly extends the life span of an antiviral regimen, but it appears that most of us will develop some resistance at some point, regardless. The key seems to be holding it off as long as possible, while newer and better therapies are developed.

JK I can't find that statement anywhere in the artical you cited. Is this your personal analysis or is there something I am missing? Just looking for clarification.

What I did find in the article is part of what Ive been saying:

The authors concluded that so long as complete adherence can be maintained over the long-term, today's drug regimens appear able to suppress viral replication for more than ten years (Phillips 1999).

Dingo boy boy honey love do as you please. Your diary policing and demands are tiring. You can't always get what you want. And I'm definitely not catering to your self-imposed citation rules. I'm a bad boy and reckless yadda yadda yadda. Whatever makes you happy.

Love ya Mikey

« Last Edit: June 06, 2006, 11:49:36 PM by StrongGuy »

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

The authors concluded that so long as complete adherence can be maintained over the long-term, today's drug regimens appear able to suppress viral replication for more than ten years (Phillips 1999).

It says '' appear '' and although this statement is correct, the facts are that it can vary a lot from one individual to another. Some people can last 10 years on the same regimen while others won't go over 3 and sometimes less. I'm certain there are a lot persons here who are at both extreme with some in the middle.

I too enjoy thebody.com pro. I have not had much time to delve into research here on the set.

One thing about this site that I dearly love is that we are optimistic not despite the fact, but because we have possession of them. There is nothing to be gained by promoting or encouraging ignorance.

« Last Edit: June 06, 2006, 11:58:07 PM by jkinatl2 »

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

hey let's all try and stay cam and not put unecessary fear into the original poster or other who may read.

[/size][/size]The best way to reduce the chance of resistance is simply to adhere to your regimen as closely as possible.

There was a period in the early 90's when there was a fear in the media that resistance was developing despite HAART therapies. There is an article about it on the body, which I've forgotten to reference I know, but it said whilst the results were valid one needed to look deeper and that the survey participants were all treatment experienced and most had taken AZT monotherapy, then dual combos before moving on to the then new triple combos - not the perfect way to start treatment, and adherence was much more difficult with the new treatments.It is difficult to find any long term scientific research on triple combination therapies and whether drug resistance can/will occur if you adhere strictly to your regimen. I found an abstract for one: http://www.jaids.com/pt/re/jaids/abstract.00126334-200212153-00006.htm;jsessionid=GGKdsbzhYgtXG6n31fGcqP1CGTsG1cs12DZc0LFc9YXVvJGPRqdr!-818462210!-949856145!8091!-1, but they want $25 for the whole article. I'll be buggered if I'm gonna pay that. and a nice simple 'fact sheet' here: http://www.atdn.org/simple/resistance.html

Thank you for clarifying JK that the statement I asked about wasn't from the article and it was your statement.

JK I read both of your links and, while interesting, I don't see them backing up your statement in any way shape or form.

But they were informative nonetheless (though I heart Dr. Pierone and Dr. Daar and my hot ID doc even more.)

Love ya Mikey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

Minimising the risk of resistance It’s important to take anti-HIV drugs exactly as prescribed, by sticking rigidly to the recommended dose and timetable, and observing instructions about food. Taking too little drug (by missing or reducing doses) could allow drug levels in the blood to fall to inadequate levels, allowing viral replication to occur and increasing the risk of the emergence of resistance.

Using three or more anti-HIV drugs at once, known as combination therapy or ‘HAART’, delays resistance, because viruses that are resistant to one of the drugs may still be controlled by the others.

Studies have shown that the risk of viral load rebound is related to the lowest point to which viral load falls after starting treatment, called the ‘nadir’. The lower the nadir, the lower the risk of rebound, and therefore the risk of resistance. People whose viral load falls to, and remains below 50 copies are at a much lower risk of developing resistance. However, resistance may emerge even in these people over the longer term.

Adding or changing a single new drug in a combination which is not suppressing viral load is likely to lead to the development of drug resistance, because the impact of that single new drug is likely to be insufficient to block replication. Experts now advise that treatment changes in these circumstances should involve switching to a completely new combination, wherever possible.

Continuing with the same drugs after your viral load begins to go up can also encourage the development of resistance. This is because resistance to some drugs develops progressively; as more resistance mutations accumulate, sensitivity to the drug will fall. However, resistance to drugs emerges at different speeds. For example, 3TC, nevirapine and efavirenz resistance emerges very quickly, but d4T and ddC resistance emerges more slowly.

Perfect adherence greatly extends the life span of an antiviral regimen, but it appears that most of us will develop some resistance at some point, regardless. The key seems to be holding it off as long as possible, while newer and better therapies are developed.

Which was supported by:

<< Most HIV physicians also have experience with patients who report the same faithfulness with the same regimen, only to experience virologic failure and resistance after months or years.

We have good evidence that virus evolution, with the development of resistance mutations, continues in the bloodstream and in 'sequestered sites' in the body such as the gonads and the central nervous system, even in patients with undetectable viral loads by standard viral load assays>>

"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

I'm relatively new to this disease. I went on HAART for a year using a PI and two NNRTIs. (I'm resistant to the NRTIs.) I had great results, went to <50 within two months. My doc told me that he thought that combo would most likely last me a long time. I asked about developing resistance. He said that it was always a possibility. We only have 10 years of HAART knowledge to study. I'm pretty sure that he was only speaking about me and my situation. For people who have been on treatment longer, especially before HAART, they have a much more complicated situation as they were once on mono therapy or a two drug regimen. Their resistance patterns are probably a lot different than someone who started drug therapy in the triple-cocktail days.

IMHO, sometimes the "100% adherence = success" is a little simplistic. I think that when the docs say 100% adherence will make a success, they are saying that if you take the medication at the exact time intervals as prescribed and it gets into your blood stream as expected, it should work because it has in most people with similar situations. But, what if the medication makes you ill and you throw it up? What if it makes you ill, gives you horrible diarrhea and runs right through you not being absorbed as intended? It is my understanding that in order to get FDA approval, recommended dosages of meds only need to work in a significant majority of the population. So let's say you are one of those people who is not as sensitive to the meds as the majority, and you happen to have orange juice (which shouldn't affect the absorption in most, but could in you), and the virus gets a little window where it can mutate. Here you are thinking that you are on-track when actually you are not. My point it that there are no absolutes in medicine. The docs and the scientists take the knowledge they have and try to apply it to our individual situations. For many it will work, but not necessarily everyone. When I asked my near-retirement orthopaedist why he does surgery on one type of patient, prescription drugs on others, and physical therapy on yet another group, he replied, "Even patients with the same diagnosis are different people. Medicine is as much of an art as it is a science."

HIV therapy does fail...if it didn't then HIV therapy would have led to the cure. Yes, it is true that strict adherence might lead to fewer resistance variants, but is what the medical community doing enough...from the answers here, it must be "no".

While it is less likely to get resistance based on exact adherence to therapy, the result is not complete eradication. Therefore by extraction, current therapy is not good enough. I agree it is futile to blame patients for non-adherence as that deflects the blame of the failure of current therapy from us to you.

What do we really need? A cure.

No longer can we be satisfied with treatments that prolong the disease. What is required is a cure, In the absence of that we require viable therapy. New targets for drug therapy represent good progress, but are not the final solution. I'm not trying to burst anyone's balloon here - therapy is better than it was. However, therapy is a long way from where it needs to be. Erradi cation, and not the suppression of virus, is what is needed. We can slap ourselves on the back and claim we have made a difference and blame patients if we like. However, despite our best efforts the virus remains out there and therefore our best efforts are not enough. The time for viral suppression is over. Eradication has to be our buzz-word. While I champion the efforts of new drug targets, this merely perpetuates the problem and doesn't solve it.

Is current HAART useless? No. Could we do better? You betcha!

I agree with the pessimistic voices here....that HAART is good but even with strict adherence it isn't the answer. Erradi cation in a manner we haven't tried is. I advocate all therapies that look at that.

It's time for an end to the hitting of moles at the carnival. Time to make a difference to the disease.

R

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